1. Technical Field
The technical field relates to a biomarker for human liver cancer.
2. Background
MicroRNAs (miRNAs) are an abundant class of short endogenous RNAs with approximately 22 nucleotides. MiRNAs act as post-transcriptional regulators of gene expression by base-pairing with their target mRNAs, resulting in the degradation of target mRNA or inhibition of the target mRNA expression.
Several studies show that the expression of miRNAs is aberrant in cancer cells. Genome-wide studies also reveal that miRNAs are present in chromosome regions exhibiting cancer-related loss of heterozygosity. In several cancer cell lines, the expression of miRNAs has been observed to be suppressed. It is suggested that miRNAs suppress tumor formation through inhibiting the oncogene expression and modulating genes involved in cell apoptosis or differentiation. The miRNAs functioning like tumor suppressor genes are also named “tumor suppressor miRNA”. It has been reported that for 68% of chronic lymphocytic leukemia (CLL) patients having deleted or suppressed miR-15 and miR-16; miR-143 and miR-145 showed lower expression levels in colon and lung cancer tissues than corresponding normal tissues; and miRNA let-7 was suppressed in lung cancer cells and a poor prognosis of lung cancer may be detected by down regulation of miRNA let-7.
Studies have shown that DNA methylation plays a role in tumor suppressor miRNAs modulation. DNA methylation refers to the conversion of cytosine to 5-methylcytosine in CpG dinucleotides by DNA methyltransferase. CpG dinucleotides are commonly rich at 5′-terminal regions, also termed “CpG sites”. Studies show that, in about 70% of human genes, CpG sites can be found in promoter regions. As CpG sites in promoter regions are hypermethylated, it has been suggested that the encoded genes in the down stream may be inhibited to precede transcription and therefore the genes are not expressed. Thus, it has been suggested that hypermethylated CpG sites can be recognized by some methyl binding proteins accompanied with histone deacetylase (HDAC) and co-repressor so as to change chromosomal structures and form inactive heterochromatins. Several studies show that aberrant DNA methylation occurs in early cancer stages, which may cause tumor suppressor genes not expressed. Recent studies show that DNA methylation not only inhibits tumor suppressor gene expression but also decreases tumor suppressor miRNA expression.